Research Paper Volume 12, Issue 13 pp 13318—13337

Subtype-specific risk models for accurately predicting the prognosis of breast cancer using differentially expressed autophagy-related genes

Baoai Han1,2,3,4, *, , He Zhang1,2,3,4, *, , Yuying Zhu1,2,3,4, , Xingxing Han1,2,3,4, , Zhiyong Wang1,2,3,4, , Zicong Gao1,2,3,4, , Yue Yuan1,2,3,4, , Ruinan Tian1,2,3,4, , Fei Zhang1,2,3,4, , Ruifang Niu1,2,3,4, ,

  • 1 Public Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China
  • 2 Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
  • 3 Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
  • 4 Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin 300060, China
* Equal contribution

Received: February 2, 2020       Accepted: May 25, 2020       Published: July 10, 2020
How to Cite

Copyright © 2020 Han et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Emerging evidence suggests that the dysregulation of autophagy-related genes (ARGs) is coupled with the carcinogenesis and progression of breast cancer (BRCA). We constructed three subtype-specific risk models using differentially expressed ARGs. In Luminal, Her-2, and Basal-like BRCA, four- (BIRC5, PARP1, ATG9B, and TP63), three- (ITPR1, CCL2, and GAPDH), and five-gene (PRKN, FOS, BAX, IFNG, and EIF4EBP1) risk models were identified, which all have a receiver operating characteristic > 0.65 in the training and testing dataset. Multivariable Cox analysis showed that those risk models can accurately and independently predict the overall survival of BRCA patients. Comprehensive analysis showed that the 12 identified ARGs were correlated with the overall survival of BRCA patients; six of the ARGs (PARP1, TP63, CCL2, GAPDH, FOS, and EIF4EBP1) were differentially expressed between BRCA and normal breast tissue at the protein level. In addition, the 12 identified ARGs were highly interconnected and displayed high frequency of copy number variation in BRCA samples. Gene set enrichment analysis suggested that the deactivation of the immune system was the important driving force for the progression of Basal-like BRCA. This study demonstrated that the 12 ARG signatures were potential multi-dimensional biomarkers for the diagnosis, prognosis, and treatment of BRCA.


BRCA: Breast cancer; ARG: Autophagy-related gene; DEARGs: Differential-expressed autophagy-related gene; OS: Overall survival; GSEA: Gene set enrichment analysis.